Influence of CYP3A5 genetic polymorphism on tacrolimus metabolism in renal transplant recipients

Objective To study the influence of CYP3A5 genetic polymorphism on tacrolimus metabolism in renal transplant recipients.Methods Fifty patients transplanted with planted cadaver kidney receiving the triple immunosuppressive (taorolimus+mycophenolate mofetil+prednison) were grouped according to CYP3A5 genotype (.1/.1,.1/.3,*3/*3).The initial dose of tacrolimus was 0.15 mg/(kg·d)and the dosage was adjusted according to the blood concentration to a target therapeutic window.Polymerase chain reaction restrict fragment length polymorphism (PCR-RFLP) was performed to genotype CYP3A5.Results Concen-tration-to-dose ratio (CO/D,whereby CO is trough level and D is daily dose per weight) could be calculated on 7th day and on 1,3 and 6 month.The CYP3A5 *3/*3 group had the largest CO/ D and the CYP3A5 *1/*1 group had the smallest CO/D.The statistical significant difference (P<0.05) was found among the three groups.Conclusion This study demonstrates that genetic polymorphism of CYP3A5 are associated with the initial tacrolimus requirments in renal transplant recipients.Patients with the CYP3A5 *1/*1 genotype may need to be given a higher dose of tacrolimus to reach target blood concentration compared with those with the CYP3A5 *3/*3 genotype.Genotyping prior to transplantation may help to assess the initial daily dose required by individual patients for adequate immunosupression. Key words: kidney transplantation; Genetic polymorphism; Tacrolimus; CYP3A5 genotype